Vascular graft replacement has come to be performed in recent years as surgical treatment for trauma and vascular diseases such as atherosclerosis, but artificial blood vessels have not been realized for small blood vessels with diameters of 5 mm and less. The reason is that obstruction due to thickening of the tunica intima of vascular grafts or thrombus formation cannot be prevented, because of the poor biocompatibility of artificial materials. The major bypass or vascular replacement technique currently used for elastic arteries such as coronary artery and lower leg peripheral arteries is autologous vein grafting. However, approximately 20-30% of all patients requiring vascular replacement do not have suitable blood vessels and are not candidates for autologous vein grafting.
In recent years, it has been attempted to coat extracellular matrixes such as collagen onto the lumen surfaces of artificial vessels made of synthetic fibers worked into small diameters (Dacron/polyurethane/drawn polytetrafluoroethylene), or onto the lumen surfaces of tubular structures formed from bioabsorbable synthetic polymers (for example, polyglycolic acid, polylactic acid, poly ε-caprolactam and the like), in order to provide them with a cell adhesion property, and to culture endothelial cells on those extracellular matrixes. However, small-diameter artificial vessels have not been realized because the endothelial cells do not become stably anchored to the extracellular matrix, or the artificial vessels undergo intimal thickening.
The blood vessel wall damage that occurs due to endothelial thickening causes smooth muscle cells near the endothelium to undergo a phenotypic change from the normal contractile to synthetic type, thus promoting growth and organization and extending the lesion. Numerous methods of culturing vascular smooth muscle cells have been investigated, as basic research on vascular smooth muscle. Examples thereof include a method of culturing solution containing insulin-like growth factor-I on a laminin-coated culture dish (for example, Patent document 1), and a method of fixing smooth muscle cells onto fibronectin-coated glass and applying shear flow stress for culturing, as a method that takes into account the orientation of the smooth muscle cells (for example, Patent document 2).
The present inventors have also developed a crosslinked elastin article having water-soluble elastin crosslinked with a water-soluble crosslinking agent, which can be applied as a biomaterial for regenerative medicine (Patent document 3). In this method, the crosslinked elastin article is utilized as a culture substrate for regenerative medicine, and embryonic stem (ES) cells, somatic stem cells, mesenchymal stem cells or the like are cultured on a film surface or tube interior made therefrom, to form organs having desired shapes. Culturing of neuroblastoma cells has been carried out using elastin films produced from crosslinked elastin articles, but no biomaterial has been disclosed with special affinity between elastin and vascular smooth muscle cells.
Since most cells in the body are present at sites that are subject to mechanical forces, dynamic culturing methods are also known whereby the cell-growing surface is expanded and contracted in order to accomplish cell culturing with growth under conditions similar to in vivo conditions (Non-patent document 1).    [Patent document 1] Japanese Unexamined Patent Publication No. 2002-335955    [Patent document 2] Japanese Patent Public Inspection No. 2002-531118    [Patent document 3] WO 02/096978    [Non-patent document 1] K. Naruse, T. Yamada, M. Sokabe, Am. J. Physiol. 274: H1532-1538 (1998) Involvement of SA channels in orienting response of cultured endothelial cells to cyclic stretch